In the present study, we investigated the role of NADPH oxidase in F (fructose)-rich-diet-induced hepatic OS (oxidative stress) and metabolic changes, and their prevention by apocynin co-administration. Wistar rats were fed for 21 days on (i) a control diet, (ii) a control diet plus 10% F in the drinking water, (iii) a control diet with apocynin in the drinking water (CA) and (iv) F plus apocynin in the drinking water (FA). Glycaemia, triglyceridaemia, NEFAs (non-esterified fatty acids) and insulinaemia were determined. In the liver, we measured (i) NADPH oxidase activity, and gene and protein expression; (ii) protein carbonyl groups, GSH and TBARSs (thiobarbituric acid-reactive substances); (iii) catalase, CuZn-SOD (superoxide dismutase) and Mn-SOD expression; (iv) liver glycogen and lipid content; (v) GK (glucokinase), G6Pase (glucose-6-phosphatase) and G6PDH (glucose-6-phosphate dehydrogenase) activities; (vi) FAS (fatty acid synthase), GPAT (glycerol-3-phosphate acyltransferase), G6Pase and G6PDH, IL-1β (interleukin-1β), PAI-1 (plasminogen-activator inhibitor-1) and TNFα (tumour necrosis factor α) gene expression; and (vii) IκBα (inhibitor of nuclear factor κB α) protein expression. F-fed animals had high serum TAG (triacylglycerol), NEFA and insulin levels, high liver NADPH oxidase activity/expression, increased OS markers, reduced antioxidant enzyme expression, and increased glycogen, TAG storage and GK, G6Pase and G6PDH activities. They also had high G6Pase, G6PDH, FAS, GPAT, TNFα and IL-1β gene expression and decreased IκBα expression. Co-administration of apocynin to F-fed rats prevented the development of most of these abnormalities. In conclusion, NADPH oxidase plays a key role in F-induced hepatic OS production and probably also in the mechanism of liver steatosis, suggesting its potential usefulness for the prevention/treatment of T2DM (Type 2 diabetes mellitus).
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August 10 2012
Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system Available to Purchase
María Cecilia Castro;
María Cecilia Castro
1
*CENEXA – Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA), Centro Colaborador OPS/OMS para Diabetes, 1900 La Plata, Argentina
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Flavio Francini;
Flavio Francini
1
*CENEXA – Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA), Centro Colaborador OPS/OMS para Diabetes, 1900 La Plata, Argentina
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Guillermo Schinella;
Guillermo Schinella
†Farmacología Básica, Universidad Nacional de La Plata, 1900 La Plata, Argentina
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Claudia Inés Caldiz;
Claudia Inés Caldiz
‡CIC – Centro de Investigaciones Cardiovasculares (UNLP-CONICET LA PLATA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 1900 La Plata, Argentina
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María Guillermina Zubiría;
María Guillermina Zubiría
§IMBICE – Instituto Multidisciplinario de Biología Celular (CONICET LA PLATA-CICPBA), 1900 La Plata, Argentina
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Juan José Gagliardino;
Juan José Gagliardino
1
*CENEXA – Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA), Centro Colaborador OPS/OMS para Diabetes, 1900 La Plata, Argentina
Correspondence: Dr Juan J. Gagliardino (email [email protected]).
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María Laura Massa
María Laura Massa
*CENEXA – Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET LA PLATA), Centro Colaborador OPS/OMS para Diabetes, 1900 La Plata, Argentina
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Publisher: Portland Press Ltd
Received:
December 16 2011
Revision Received:
June 25 2012
Accepted:
June 28 2012
Accepted Manuscript online:
June 28 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (12): 681–692.
Article history
Received:
December 16 2011
Revision Received:
June 25 2012
Accepted:
June 28 2012
Accepted Manuscript online:
June 28 2012
Citation
María Cecilia Castro, Flavio Francini, Guillermo Schinella, Claudia Inés Caldiz, María Guillermina Zubiría, Juan José Gagliardino, María Laura Massa; Apocynin administration prevents the changes induced by a fructose-rich diet on rat liver metabolism and the antioxidant system. Clin Sci (Lond) 1 December 2012; 123 (12): 681–692. doi: https://doi.org/10.1042/CS20110665
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